open access: Nature Reviews: Key Advances in Medicine

the fourth are not yet available. Moreover,
two other studies of different tyrosine kinase
inhibitors are ongoing in patients with SSc:
one open-label phase IIa study using nilotinib
and another open-label phase I/II study
using dasatinib.
‘‘ …will new mechanistic
insights lead to new medicines
for SSc?
’’
Results from the imatinib trials published
in 2011 were somewhat disappointing in
terms of the tolerance and efficacy of the
drug. Spiera et al. 5 conducted a phase IIa,
open-label, single-arm clinical trial in 30
patients with diffuse SSc who were treated
with imatinib (400 mg per day) over
12 months. Mean Rodnan skin score (MRSS)
decreased by 6.6 points (or by 22.4%) at
12 months (P = 0.001). 5 Pulmonary function
was also tested, with forced vital capacity
(FVC) improving by 6.4% predicted
(P = 0.008), whereas the diffusion capacity
remained stable. 5 Six patients withdrew from
the study, two because of non compliance,
four because of adverse events (including
one who died after 11 months). 5 In total, 171
adverse events of various grades were identified,
the most common being edema, which
was observed in 80% of patients. 24 serious
adverse events were identified, two of which
were attributed to the study medication. 5 The
authors concluded that imatinib has acceptable
safety and toler ability, and suggest it has
potential efficacy for cutaneous and pulmonary
manifestations of SSc. 5 However, other
studies did not replicate these findings.
In their phase I/IIa pilot study, Khanna
and colleagues 6 recruited 20 patients with
SSc-related interstitial lung disease (ILD)
who had FVC 0.05) and MRSS
(of 3.9 units; P